Cell shape change and motility are critical components of cancer cell invasion and metastasis, as well as angiogenesis, all major rate-limiting steps in cancer progression. Cell movement is also involved in immune cell function, tissue repair and embryonic development. With an understanding of the signal transduction pathways that lead to cell motility comes the potential for new kinds of therapeutic intervention in cancer progression that may complement those directed against cell growth. The proposed study on the drug-based discovery of protein targets involved in the signaling to cell migration are highly relevant to understanding and gaining therapeutic control over cancer. Cancer cell invasion and metastasis are by definition processes that involve the acquisition by tumor cells of the ability to move. This study may help further elucidate the mechanisms of angiogenesis, a critical step in early tumor progression involving cell shape change and motility in addition to cell proliferation, as well as wound healing and other processes of tissue dynamics and development. Using a combination of chemical and cellular methods, the goal of the proposed research is to contribute fundamentally to an understanding of the mechanisms of tissue development in normal and pathological situations, especially the control of cell migration. The proposed studies are highly relevant to understanding and gaining therapeutic control over cancer. This research will focus on the characterization of a novel inhibitor of cell motility and proliferation we have discovered and the identification of other new organic molecules that perturb cell migration. It will also entail the isolation of the cellular targets of these small molecules. The screening of compound libraries may lead to the direct discovery of potential drugs in addition to providing information on-protein targets for subsequent drug development. The epithelial cell model we are using is a tractable and robust system for studying cell motility, allowing for rapid analysis of parallel experiments and quantitative measurement of motility rates and cell morphologies from digital images. It will provide information on targets involved not only in cell movement itself but also in the regulation of motility by cell-cell interactions and adhesion. Therefore, in addition to gaining knowledge of the signaling pathways leading to cell motility, this study may provide deeper insight into the systems that fail when malignant cells break off from normally cohesive tissue, becoming invasive and metastatic, such as in carcinomas and other solid tumors.